ABSTRACT
A 73-year-old man with lung squamous cell carcinoma was administered carboplatin + nab-paclitaxel + pembrolizumab for four cycles. Subsequently, he presented with multiple purpuras on his extremities, joint swelling on his fingers, abdominal pain, and diarrhea, accompanied by acute kidney injury (AKI), increased proteinuria, hematuria, and elevated C-reactive protein levels. Skin biopsy showed leukocytoclastic vasculitis as well as IgA and C3 deposition in the vessel walls. Based on these findings, the patient was diagnosed with IgA vasculitis as an immune-related adverse event (irAE) induced by carboplatin + nab-paclitaxel + pembrolizumab. After discontinuation of pembrolizumab and glucocorticoids, the symptoms immediately resolved. Regular monitoring of skin, blood tests, and urinalysis are necessary, and the possibility of irAE IgA vasculitis should be considered in cases of purpura and AKI during treatment with immune checkpoint inhibitors.
Subject(s)
Albumins , Antibodies, Monoclonal, Humanized , Antineoplastic Combined Chemotherapy Protocols , Carboplatin , Carcinoma, Squamous Cell , Lung Neoplasms , Paclitaxel , Humans , Male , Aged , Carboplatin/adverse effects , Carboplatin/administration & dosage , Carboplatin/therapeutic use , Paclitaxel/adverse effects , Paclitaxel/administration & dosage , Paclitaxel/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/administration & dosage , Lung Neoplasms/drug therapy , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Carcinoma, Squamous Cell/drug therapy , Albumins/adverse effects , Albumins/administration & dosage , IgA Vasculitis/chemically induced , IgA Vasculitis/diagnosis , Immunoglobulin A , Immune Checkpoint Inhibitors/adverse effectsABSTRACT
Keloids are benign fibroproliferative skin tumors caused by aberrant wound healing that can negatively impact patient quality of life. The lack of animal models has limited research on pathogenesis or developing effective treatments, and the etiology of keloids remains unknown. Here, we found that the characteristics of stem-like cells from keloid lesions and the surrounding dermis differ from those of normal skin. Furthermore, the HEDGEHOG (HH) signal and its downstream transcription factor GLI1 were upregulated in keloid patient-derived stem-like cells. Inhibition of the HH-GLI1 pathway reduced the expression of genes involved in keloids and fibrosis-inducing cytokines, including osteopontin. Moreover, the HH signal inhibitor vismodegib reduced keloid reconstituted tumor size and keloid-related gene expression in nude mice and the collagen bundle and expression of cytokines characteristic for keloids in ex vivo culture of keloid tissues. These results implicate the HH-GLI1 pathway in keloid pathogenesis and suggest therapeutic targets of keloids.